Ensartinib for Cancer

Not currently recruiting at 140 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 agents, Anti-cancer agents

Disqualifiers: Pregnancy, Uncontrolled infection, Organ transplant, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well the drug ensartinib works for children and young adults with certain recurring or hard-to-treat cancers, such as solid tumors or non-Hodgkin lymphoma, that have specific genetic changes. Ensartinib may help by blocking enzymes necessary for cancer cell growth. Suitable candidates for this trial have cancers with specific ALK or ROS1 genetic changes and are not responding to current treatments. Participants will take ensartinib daily and undergo various imaging tests and blood sample collections to monitor progress. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to benefit from a potentially effective therapy.

Do I have to stop taking my current medications for the trial?

Yes, you may need to stop some medications. You cannot take other anti-cancer agents, investigational drugs, or strong CYP3A4 inducers/inhibitors. If you're on corticosteroids, you must be on a stable or decreasing dose for at least 7 days before enrolling. Anti-GVHD agents post-transplant are also not allowed. Check with the study team for specific guidance on your medications.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before enrolling. You cannot be on other anti-cancer agents, investigational drugs, or strong inducers or inhibitors of CYP3A4. If you're on corticosteroids, you need to be on a stable or decreasing dose for at least 7 days before enrolling.

Is there any evidence suggesting that ensartinib is likely to be safe for humans?

Research has shown that ensartinib is generally well-tolerated by patients with certain types of cancer. In studies involving patients with ALK-positive non-small cell lung cancer, the FDA approved ensartinib, indicating its safety for that condition. However, like any treatment, it can have side effects.

In a safety study, 44% of patients taking ensartinib experienced side effects based on lab results. These side effects can vary, so discussing them with a healthcare provider is advisable. Researchers are also studying ensartinib for other types of cancer, which means they are still learning about its safety for those conditions. Since this trial is in an early phase, the safety of ensartinib for the specific conditions under study is still being assessed. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Ensartinib is unique because it targets specific genetic mutations in cancer cells, making it a potential game-changer for patients with these mutations. Unlike traditional chemotherapy, which attacks both healthy and cancerous cells, ensartinib aims directly at cancer cells, potentially reducing side effects. Researchers are excited about its ability to offer a more personalized treatment approach, which could lead to better outcomes for patients with fewer adverse effects.

What evidence suggests that ensartinib might be an effective treatment for cancer?

Research has shown that ensartinib, the treatment under study in this trial, effectively treats certain cancers with specific genetic changes. One study found that ensartinib significantly increased the time patients lived without their disease worsening compared to another treatment. Specifically, the study reported a hazard ratio of 0.56, indicating a lower risk of cancer progression for patients on ensartinib. In another case, a patient with a type of lung cancer improved after three months of treatment, with their disease remaining stable for six months. Ensartinib is particularly effective against cancers with ALK-positive changes, effectively stopping or slowing the growth of cancer cells. ^{1 2 6 7 8}

Who Is on the Research Team?

Meredith S Irwin

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for children and young adults up to 21 years old with advanced solid tumors, non-Hodgkin lymphoma, or histiocytic disorders that have specific genetic changes (ALK or ROS1) and haven't responded to previous treatments. Participants need normal organ function, must be able to swallow capsules, and can't have had ensartinib before.

Inclusion Criteria

I am between 12 and 21 years old.

I have had a stem cell transplant, with or without full body radiation.

I have recovered from side effects of my previous cancer treatments.

Exclusion Criteria

You have had an organ transplant in the past.

I do not have any infections that are currently uncontrolled.

I am currently taking or have taken anti-cancer medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive ensartinib orally once daily on days 1-28. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Up to 2 years

Regular visits for imaging and blood sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

30 days

1 visit (in-person)

Long-term follow-up

Participants are monitored for progression-free survival and changes in tumor genomic profile

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Ensartinib

Trial Overview The study tests how well the drug ensartinib works on patients with certain recurrent or refractory cancers. It includes various imaging studies like MRIs and bone scans to monitor the effects of the treatment which aims at blocking enzymes important for cancer cell growth.

How Is the Trial Designed?

Group I: Treatment (ensartinib) Experimental Treatment 11 Interventions

Patients receive ensartinib PO QD on days 1-28. Cycles repeat every 28 days for 2 years (up to 26 cycles) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, PET scan, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study.

Ensartinib is already approved in United States for the following indications:

Approved in United States as Ensacove for:

• ALK-positive non-small cell lung cancer

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Children's Oncology Group

Collaborator

Trials

467

Recruited

241,000+

Published Research Related to This Trial

An 82-year-old patient with chemotherapy-naive metastatic castration-resistant prostate cancer showed a long-term response to a very low dose of 40 mg enzalutamide daily, indicating that lower doses may still be effective.

Using lower doses of enzalutamide not only reduces the risk of side effects but could also lower healthcare costs and improve access to treatment, suggesting a need for further studies on the efficacy of these reduced doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep and ongoing response of castrate-resistant prostate cancer on very low-dose enzalutamide in an elderly chemotherapy-naïve patient: a case report. Boerrigter, E., Havenith, T., van Erp, NP., et al.[2021]

Sorafenib is an effective treatment for patients with unresectable hepatocellular carcinoma (HCC) and advanced renal cell carcinoma (RCC), and is currently being tested in various other cancers, including differentiated thyroid cancer and metastatic breast cancer.

Common side effects of sorafenib, such as skin issues, diarrhea, fatigue, and hypertension, can be managed effectively through early recognition, patient education, and communication with healthcare teams, which helps patients maintain their full dosage during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of common adverse events in patients treated with sorafenib: nurse and pharmacist perspective. Walko, CM., Grande, C.[2018]

Enzalutamide significantly improves overall survival and radiographic progression-free survival in men with metastatic, castration-resistant prostate cancer (mCRPC), as shown in two major randomized trials (AFFIRM and PREVAIL) involving patients who had previously undergone chemotherapy and those who were chemotherapy naive.

While enzalutamide is generally safe and effective, it can cause side effects like fatigue and has specific safety concerns, such as an increased risk of seizures and falls, particularly in older patients (≥ 75 years).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of enzalutamide in men with metastatic, castration-resistant prostate cancer. Graff, JN., Gordon, MJ., Beer, TM.[2021]

In a long-term study of 67 patients with hormone-naïve prostate cancer, enzalutamide monotherapy resulted in a 100% prostate-specific antigen (PSA) response rate at 97 weeks for those who remained on treatment, indicating its strong efficacy.

The treatment was well-tolerated with minimal negative effects on total-body bone mineral density, although common side effects included gynecomastia and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Efficacy and Safety of Enzalutamide Monotherapy in Hormone-naïve Prostate Cancer: 1- and 2-Year Open-label Follow-up Results. Tombal, B., Borre, M., Rathenborg, P., et al.[2021]

In a study involving 58 patients with metastatic renal carcinoma, sorafenib demonstrated a median progression-free survival of 7.5 months, indicating its efficacy as a second-line therapy.

However, the treatment was associated with a high rate of grade 3/4 adverse events (64%), including skin rash and hand-foot syndrome, suggesting that while effective, sorafenib may lead to significant toxicity in a broader patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sorafenib for metastatic renal cancer: the Princess Margaret experience. Riechelmann, RP., Chin, S., Wang, L., et al.[2018]

Sorafenib, the first multikinase inhibitor approved for renal cell cancer, significantly improves progression-free survival compared to placebo, highlighting its efficacy in treating advanced RCC.

However, patients experienced higher rates of adverse events with sorafenib, necessitating effective management strategies to maintain quality of life and optimize treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experience with sorafenib and adverse event management. Bellmunt, J., Eisen, T., Fishman, M., et al.[2018]

In a study of 670 metastatic renal cell carcinoma patients, those treated with sunitinib had a significantly better overall survival (31.7 months) compared to those treated with pazopanib (20.6 months), suggesting sunitinib may be the more effective first-line treatment.

While sunitinib was associated with more side effects like mucositis and hand-foot syndrome, pazopanib led to a higher incidence of hepatotoxicity, indicating that the choice of treatment may also depend on the patient's tolerance to these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line sunitinib or pazopanib in metastatic renal cell carcinoma: The Canadian experience. Lalani, AA., Li, H., Heng, DYC., et al.[2022]

A phase 2b trial showed that adding sorafenib to capecitabine significantly improved progression-free survival in patients with HER2-negative advanced breast cancer, with a median PFS of 6.4 months compared to 4.1 months for placebo.

The ongoing phase 3 RESILIENCE trial aims to confirm these findings with a target enrollment of approximately 519 patients, focusing on the safety and efficacy of the sorafenib and capecitabine combination, while implementing a dosing strategy to manage potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 3 tRial comparing capecitabinE in combination with SorafenIb or pLacebo for treatment of locally advanced or metastatIc HER2-Negative breast CancEr (the RESILIENCE study): study protocol for a randomized controlled trial. Baselga, J., Costa, F., Gomez, H., et al.[2021]

A total of 3120 adverse event cases related to avapritinib were reported to the FDA, with 44% occurring within the first 30 days of treatment, highlighting the importance of monitoring patients closely during this period.

The study found that elderly male patients are at a higher risk for serious adverse events, indicating that clinicians should exercise caution when prescribing avapritinib to this demographic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A post-marketing pharmacovigilance study of avapritinib: Adverse event data mining and analysis based on the United States Food and Drug Administration Adverse Event Reporting System database. Rong, L., Xie, M., Jiang, M., et al.[2023]

Lenvatinib is an effective multikinase inhibitor approved for treating radioiodine-refractory differentiated thyroid cancer and advanced renal cell carcinoma, showing favorable efficacy in various malignancies.

While lenvatinib has beneficial effects, it is associated with common adverse events like hypertension and fatigue, necessitating careful monitoring and management to enhance patient quality of life and treatment adherence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing the adverse events associated with lenvatinib therapy in radioiodine-refractory differentiated thyroid cancer. Cabanillas, ME., Takahashi, S.[2019]

Enzalutamide is an effective oral androgen receptor inhibitor for treating castration-resistant prostate cancer (CRPC), showing significant benefits in overall survival and progression-free survival in large clinical trials, including the AFFIRM trial with 1,199 patients.

The drug was well tolerated in both chemotherapy-naïve and post-chemotherapy patients, demonstrating similar pharmacokinetic and anti-tumor activity profiles across different populations, leading to its approval by regulatory agencies in the US and Japan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Enzalutamide-a novel androgen receptor inhibitor that provides treatment options for patients with castration-resistant prostate cancer]. Maeda, H., Saito, A.[2021]

Encorafenib, in combination with cetuximab, has been shown to improve survival rates in patients with BRAFV600E-mutant metastatic colorectal cancer compared to conventional chemotherapy, highlighting its efficacy as a targeted therapy.

This treatment regimen is generally better tolerated than traditional cytotoxic therapies, but it can lead to unique adverse events that require careful management by healthcare professionals, particularly nurses, who play a crucial role in patient care and education.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nursing care and management of adverse events for patients with BRAFV600E-mutant metastatic colorectal cancer receiving encorafenib in combination with cetuximab: a review. Fowler, M., Tobback, H., Karuri, A., et al.[2023]

In a study of 44 patients with metastatic renal cell carcinoma, sorafenib showed promising antitumor activity, with a 48% rate of complete or partial responses and 64% of patients experiencing progression-free survival of 6 months or more.

Most patients were able to safely escalate their dose of sorafenib from 400 mg to 600 mg or 800 mg twice a day, with manageable side effects such as hypertension and skin reactions, indicating that higher doses can be tolerated and may enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of intrapatient dose-escalated sorafenib in patients with metastatic renal cell carcinoma. Amato, R., Zhai, J., Willis, J., et al.[2022]

Regorafenib (REG) was associated with a high incidence of renal adverse drug reactions (ADRs), accounting for 93.1% of 379 reports, with significant safety signals for conditions like chromaturia, hydronephrosis, and acute kidney injury.

Encorafenib (ENC) also showed potential renal toxicity, particularly with acute kidney injury and dysuria, indicating that both drugs may pose risks to kidney health in patients with metastatic colorectal cancer (mCRC) that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Renal Disorders with Oral Tyrosine Kinase Inhibitors in Metastatic Colorectal Cancer: An Analysis from the FDA Adverse Event Reporting System Database. Russo, G., Barbieri, MA., Sorbara, EE., et al.[2023]

A validated method for quantifying enzalutamide and its active metabolite, N-desmethylenzalutamide, was developed using mass spectrometry, ensuring accurate measurements in patients with metastatic castration-resistant prostate cancer.

The method demonstrated high precision and accuracy, with stability of the compounds confirmed for extended periods, making it suitable for both clinical studies and routine patient monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and Validation of a Bioanalytical Method to Quantitate Enzalutamide and its Active Metabolite N-Desmethylenzalutamide in Human Plasma: Application to Clinical Management of Patients With Metastatic Castration-Resistant Prostate Cancer. Benoist, GE., van der Meulen, E., van Oort, IM., et al.[2021]

Citations

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Breaking news! Ensartinib clinical study results were ... The updated data showed the good continuous results with an overall ORR as 52.6%, the disease control rate as 87.8%, the median PFS as 11.2 ...

2. becarispublishing.com becarispublishing.com/doi/10.2217/cer-2022-0066

Cost–effectiveness of ensartinib for patients with anaplastic ... The purpose of this study is to conduct the cost–effectiveness analysis of ensartinib and crizotinib in the treatment of ALK-positive NSCLC and provide ...

3. sciencedirect.com sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/ensartinib

Ensartinib - an overview | ScienceDirect Topics Ensartinib is 10-fold more potent than crizotinib for inhibiting the growth of ALK-positive lung cancer cell lines, and reported activity in a broad spectrum ...

4. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-ensartinib-alk-positive-locally-advanced-or-metastatic-non-small-cell-lung-cancer

FDA approves ensartinib for ALK-positive locally advanced ... Ensartinib demonstrated a statistically significant PFS improvement compared to crizotinib with a hazard ratio (HR) of 0.56 (95% CI: 0.40, 0.79; ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11883823/

Ensartinib for EML4-ALK-positive lung adenocarcinoma with ... After 3 months of ensartinib treatment, the patient achieved a partial response and reached stable disease at six months, which sustained for 30 ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2025/218171Orig1s000IntegratedR.pdf

218171Orig1s000 - accessdata.fda.gov the available in vitro solubility data and clinical PK and safety data of ensartinib in patients received concomitant mediations of proton pump inhibitors ...

7. drugs.com drugs.com/pro/ensacove.html

Ensacove: Package Insert / Prescribing Information In the pooled safety population [see Adverse Reactions (6.1)], based on laboratory data, 44% of patients receiving ENSACOVE experienced ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0090955624010845

Prediction of Drug–Drug Interactions with Ensartinib as a ... Ensartinib was found to be a strong time-dependent inhibitor of CYP3A for the first time based on in vitro experiments.